Cytokines and fatty liver diseases

Niederreiter, Lukas; Tilg, Herbert

doi:10.1016/j.livres.2018.03.003

Cited by 86 publications

(68 citation statements)

References 86 publications

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“…(28) A wide range of cytokines were detected in the model, and the expression of many of these was enhanced by the loading of cells with FFAs or additional dosing of LPS (Table 2). Recent review articles have highlighted a key subset of cytokines observed in the clinical disease, (37,38) and each of these we have detected in our in vitro MPS model ( Table 2). The co-cultures also exhibited a range of transcriptomic changes as compared with the PHH-only steatosis model.…”

Section: Discussionmentioning

confidence: 87%

A Microphysiological System for Studying Nonalcoholic Steatohepatitis

et al. 2019

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Nonalcoholic steatohepatitis (NASH) is the most severe form of nonalcoholic fatty liver disease (NAFLD), which to date has no approved drug treatments. There is an urgent need for better understanding of the genetic and molecular pathways that underlie NAFLD/NASH, and currently available preclinical models, be they in vivo or in vitro, do not fully represent key aspects of the human disease state. We have developed a human in vitro co‐culture NASH model using primary human hepatocytes, Kupffer cells and hepatic stellate cells, which are cultured together as microtissues in a perfused three‐dimensional microphysiological system (MPS). The microtissues were cultured in medium containing free fatty acids for at least 2 weeks, to induce a NASH‐like phenotype. The co‐culture microtissues within the MPS display a NASH‐like phenotype, showing key features of the disease including hepatic fat accumulation, the production of an inflammatory milieu, and the expression of profibrotic markers. Addition of lipopolysaccharide resulted in a more pro‐inflammatory milieu. In the model, obeticholic acid ameliorated the NASH phenotype. Microtissues were formed from both wild‐type and patatin‐like phospholipase domain containing 3 (PNPLA3) I148M mutant hepatic stellate cells. Stellate cells carrying the mutation enhanced the overall disease state of the model and in particular produced a more pro‐inflammatory milieu. Conclusion: The MPS model displays a phenotype akin to advanced NAFLD or NASH and has utility as a tool for exploring mechanisms underlying the disease. Furthermore, we demonstrate that in co‐culture the PNPLA3 I148M mutation alone can cause hepatic stellate cells to enhance the overall NASH disease phenotype.

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Section: Discussionmentioning

confidence: 87%

A Microphysiological System for Studying Nonalcoholic Steatohepatitis

et al. 2019

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“…NAFLD is considered a chronic subclinical inflammatory condition through secreting proinflammatory cytokines and chemokines by both hepatocytes and by non-parenchymal cells such as stellate cells and Kupffer cells [99]. Several inflammatory markers as well as serum levels of IL-6, IL-1, TNF-α, and C-reactive protein (CRP) have been demonstrated to be related to cardiovascular events in NAFLD [100].…”

Section: Introductionmentioning

confidence: 99%

Relationship between Heart Disease and Liver Disease: A Two-Way Street

Hadi

Vincenzo

Rossato

2020

Cells

125

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In clinical practice, combined heart and liver dysfunctions coexist in the setting of the main heart and liver diseases because of complex cardiohepatic interactions. It is becoming increasingly crucial to identify these interactions between heart and liver in order to ensure an effective management of patients with heart or liver disease to provide an improvement in overall prognosis and therapy. In this review, we aim to summarize the cross-talk between heart and liver in the setting of the main pathologic conditions affecting these organs. Accordingly, we present the clinical manifestation, biochemical profiles, and histological findings of cardiogenic ischemic hepatitis and congestive hepatopathy due to acute and chronic heart failure, respectively. In addition, we discuss the main features of cardiac dysfunction in the setting of liver cirrhosis, nonalcoholic fatty liver disease, and those following liver transplantation.

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“…The results showed that the level of CK elevated remarkably in the group that maintained on HFD only. Studies showed that the higher serum level of CK is associated with higher body fat mass, and consider as biochemical evidence of metabolic abnormality and the presence of NAFLD (20) (21) , Guggulsterone treatment resulted in lowering the level of CK, the higher the concentration result in the lower level of CK, this can be attributed to the hypolipidemic ability of guggulsterone that resulted in lower body visceral fat (19) (18) .TNF-α is used as a predictor of fibrosis in patients with Steatohepatitis (22) .The elevation in TNF-α is related to aberrant production of cytokines by adipose macrophages and Kupffer cells (23) through the activation of TLR4 in macrophages that initiates downstream signaling pathways including nuclear factor-kappa B (NF-κB) complex that play an important role in acute and chronic inflammatory conditions in response to liver damage caused by HFD (24) (25) . The treatment with guggulsterone as shown in the results had significantly decreased the elevated serum level of both TNF-α compared to the HFD group.…”

Section: Discussionmentioning

confidence: 99%

Possible Amelioration of the Severity of Nutritional Steatohepatitis by Guggulsterone in Mice

Nafeer

Zalzala²

2019

IJPS

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Non-alcoholic fatty liver disease (NAFLD) has become one of the most common chronic liver diseases worldwide, which is characterized by steatosis, inflammation, and fibrosis. The aim of this designed study is to evaluate the ability of guggulsterone to prevent high fat diet induced steatohepatitis in mice. Five groups of male mice were selected and treated as the following: group I, mice had free access to standard commercial diet and considered as control group, group II, mice were fed a specially formulated high-fat diet for 12 weeks to induce non-alcoholic liver disease, while groups III, IV and V the mice were administered high fat diet containing guggulsterone at 500, 1000 and 2000 ppm concentration respectively for 12 weeks. Maintaining mice on fat rich diet only resulted in inducing the metabolic and histological changes related to NAFLD. While the treatment with guggulsterone significantly improves the evaluated markers. These results demonstrate guggulsterone may be useful in preventing the development of steatohepatitis.

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Cytokines and fatty liver diseases

Cited by 86 publications

References 86 publications

A Microphysiological System for Studying Nonalcoholic Steatohepatitis

A Microphysiological System for Studying Nonalcoholic Steatohepatitis

Relationship between Heart Disease and Liver Disease: A Two-Way Street

Possible Amelioration of the Severity of Nutritional Steatohepatitis by Guggulsterone in Mice

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